This S10 High End Instrumentation grant application from the Mallinckrodt Institution of Radiology (MIR) at Washington University (WU) in Saint Louis, entitled ?Replacement of a 4.7-T Small-Animal MRI Scanner with a 9.4-T System?, seeks to purchase a state-of-the-art preclinical Bruker 9.4-T (400-MHz) MRI scanner with a 4- element CryoProbeTM optimized for imaging of mouse brain. Very strong institutional support is provided with a cost-sharing (matching fund) commitment of $600,000 from the Head of MIR. The requested instrument will replace an aging preclinical 4.7-T scanner built around an Agilent/Varian console now entering its second decade and Oxford Instruments magnet manufactured over three decades ago. The requested instrument will be integrated within the WU/MIR Small-Animal MR Facility, a well administered, highly client focused, collaborative, and collegial research resource whose users have logged over 6,300 scanner- hours on average each year for the past five years. This Facility is also a critical component of the Alvin J. Siteman Cancer Center, an NCI-Designated Comprehensive Cancer Center (scored as Exceptional on its last competitive renewal), as it serves as the MRI component of the Center?s Small-Animal Cancer Imaging Shared Resource. The base grant projects that support this proposal represent a wide range of applied and basic biomedical research efforts that will greatly benefit from the performance capabilities of the requested instrument. Chief amongst these performance gains are: (i) a substantial gain in signal detection sensitivity (~ 2.5x) for mouse brain MRI (and perhaps other surface-lying tissues) is provided by the CryoProbe; (ii) fast, strong gradients driven by the 500V/300A gradient power amplifiers enable improved performance of gradient-intensive pulse sequences (e.g., DBSI, EPI, GEPCI); (iii) an extensive robust optimized pulse sequence library and image reconstruction tools, including non-Cartesian k-space sampling and multi-receiver (array) capabilities, are provided by the ParaVision software operating environment, and (iv) the heart of the scanner is a modern ultra- shielded and refrigerated superconducting magnet with greatly reduced stray field (magnet center to 0.5mT, 2.0/3.0 m radial/axial), no liquid nitrogen, and essentially zero liquid helium boil off, substantially reducing maintenance requirements (weekly/monthly cryogen fills) with concomitant cost and time & effort savings. This S10 HEI grant application thoroughly documents how the requested preclinical 9.4-T MRI scanner and CryoProbe will markedly and positively impact the funded research projects of the major user group.